Targeting severe asthma sub-types with a view to reducing worsening symptoms, improving asthma control, quality of life and lung function.

Phase 1

• Conditions: T2-High and T2-Low severe asthma; MedDRA version: 21.1Level: LLTClassification code 10068462Term: Eosinophilic asthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]; MedDRA version: 20.1Level: LLTClassification code 10005503Term: Blood eosinophilsSystem Organ Class: 100000004848; MedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 21.1Level: LLTClassification code 10049868Term: Asthma exacerbation prophylaxisSystem Organ Class: 100000004865

• Registration Number: EUCTR2019-003013-34-GB
• Lead Sponsor: niversity of Leicester

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-02-05
• Last Update Posted: 4 May 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 234

Inclusion Criteria

Screening Eligibility Criteria:

1. Exacerbation prone (=2 record confirmed severe exacerbations).
AND
2. Severe asthma (defined by a hospital specialist or severe asthma Multi-Disciplinary Team (MDT) (or non-English equivalent), according to the ATS/ERS consensus criterion.
3. Male and female patients aged =18 years and <80 years of age.
4. Capable of giving written informed consent.
5. Willing and able to comply with study protocol requirements.

Overarching T2-High and T2-Low criteria:

1.Male and female patients aged =18 years and <80 years of age.
2.Capable of giving written informed consent.
3.Diagnosis of severe asthma defined by a specialist Multi Disciplinary Team (MDT; or non-English equivalent) as per the ATS/ERS severe asthma guidelines (participants may be included with a lower dose of current ICS than endorsed by the ATS/ERS criteria at the discretion of the Investigator if previous high ICS dose had led to side effects.
4.Stable asthma therapy for at least 1 month before screening.
5.History of ‘exacerbation prone asthma’ defined as = two record confirmed severe exacerbations within 12 months of MDT initial pre-screening review. Defined as worsening asthma symptoms necessitating one or more of the following:

(i)Use of systemic steroids (tablets, suspension or injection) or an increase in systemic steroids (for those on stable maintenance steroids) for =3 days.
(ii)A new prescription of antibiotics because of worsening asthma/airways disease for =3 days.
(iii)Both (i) and (ii)
(iv)An admission to hospital because of asthma, or an emergency department requiring systemic steroids (tablets, suspension or injection) or antibiotics.

[If any of the above are identified >7 days apart, these would be defined as separate/new exacerbation events].

7.Willing and able to comply with study protocol requirements.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

1.Current or within the last 6 months (or maximum relevant wash out period, whichever is longer) participation in an investigational drug or device trial at the time of screening.
2.Patients who are planning to take more than a 21 day consecutive holiday during the trial period.
3.Have received treatment with biologics such as omalizumab, mepolizumab, reslizumab, benralizumab or dupilumab within four months or five half-lives (whichever is longer) prior to screening.
4.Recent treatment with bronchial thermoplasty, defined as completion of all thermoplasty treatment sessions within 6 months of screening.
5.Patients who have been hospitalised or required a new prescription of high-dose (=10mg prednisolone/day) oral corticosteroid (OCS) therapy within 4 weeks of the screening visit.
6.Recent (within 4 weeks of screening) or current lower respiratory tract infection requiring antibiotics (this excludes antibiotics taken for other purposes other than asthma exacerbations).
7.Acute illness other than asthma which, in the investigator’s opinion, may compromise the well-being of the patient or study endpoint assessments at the start of the study.
8.History of unstable or severe cardiac, hepatic, or renal disease, or other medically significant illness which the investigator believes would be a contraindication to study participation.
9.Current smoking within the past year or a prior smoking history of =15 pack-years (including e cigarettes).
10.Patients with a body mass index (BMI) = 17 or = 45 kg/m2.
11.History of human immunodeficiency virus (HIV) or hepatitis B or C.
12.History of malignancy of any organ system (other than localised basal cell carcinoma of the skin), treated or untreated, currently or within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
13.History (or suspected history) of alcohol or substance abuse as defined by the Diagnostic and Statistical manual of mental Disorders (5th edition) substance use disorders guidelines within two years of screening.
14.If female, is pregnant or lactating or intends to become pregnant during the study period where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
15.Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using 2 highly effective forms of contraception during dosing of study treatment and for a minimum of 1 month after their last treatment.
16.Males unwilling to use effective methods of contraception during dosing of trial treatment and for at least 3 months after their last dose.
17.Patients with clinically significant laboratory abnormalities (not associated with the study indication) at screening including (but not limited to):
•AST or ALT>2.0 x upper limit of normal (ULN) or total bilirubin >1.3 X ULN at screening (with the exception of patients with Gilberts syndrome where suitability for inclusion will be left to the discretion of the local investigator).
•Estimated Glomerular Filtration Rate (eGFR) by the MDRD equation <60 mL/minute/1.73 m2 at screening.

Additional Exclusion criteria for T2-LOW only:

1.Patients who are unwilling to stay out of the sun or wear sun block.
2.History of myasthenia gravis or systemic lupus erythematosus.
3.Prior history of ‘severe’ (as defined by the patient), gastrointestinal intolerance to tetracyclines.
4.Documented drug allergy to/

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified